GB898292A - Improvements in or relating to steroids and the manufacture thereof - Google Patents

Abstract

The invention comprises compounds of the formula <FORM:0898292/IV (b)/1> <FORM:0898292/IV (b)/2> <FORM:0898292/IV (b)/3> <FORM:0898292/IV (b)/4> wherein R is H or a hydrocarbyl radical containing 1-12 carbon atoms, o -carboxy-lower-hydrocarbyl containing 1-12 carbon atoms, including metal salts thereof, disubstituted-amino-methylene radicals including salts thereof, R1 is hydrogen or fluorine, Y is b -hydroxymethylene or carbonyl, and Z is hydrogen, fluorine, chlorine or bromine and processes for the production thereof (a) by esterifying the corresponding 17a -hydroxy compound with an acid anhydride in the presence of an acidic esterification catalyst and then, if desired, thereafter hydrolysing any 3-enol ester formed under mild conditions with a base, (b) dehydrating the corresponding 17-hydroxy compound to produce the corresponding D 9(11)-compound, esterifying, reacting the resulting 17-acyloxy ester with N-bromoacetamide to form the 9-bromo derivative and removing the bromine atom with zinc and acetic acid, (c) converting the corresponding 17-hydroxy compound to a 17-bromoacetate ester, reacting the latter with a secondary amine to produce the 17-disubstituted aminoacetate ester, treating with an acid to form an acid salt or with an alkyl halide to form a quaternary ammonium salt. Illustrative products of the invention are 6a ,16-dimethyl - 9a - fluoro - 11b , 17a - dihydroxy - 1, 4 - pregnadiene-3,20-dione 17-acetate, the corresponding diethylaminoacetate hydrochloride, 6a , 9a - difluoro - 11b , 17a - dihydroxy - 16a - methyl - 1,4-pregnadiene-3,20-dione 17-acetate and the corresponding 4-pregnene compounds. Specifications 898,291, 898,293 and 898,294 are referred to.ALSO:Pharmaceutical compositions comprise compounds of the formula <FORM:0898292/VI/1> <FORM:0898292/VI/2> <FORM:0898292/VI/3> <FORM:0898292/VI/4> wherein R is H or a hydocarbyl radical containing 1-12 carbon atoms, o -carboxy-lower hydrocarbyl containing 1-12 carbon atoms, including metal salts thereof, disubstituted-amino methylene radicals including salts thereof, R1 is hydrogen or fluorine, Y is b -hydroxymethylene or carbonyl and Z is hydrogen, fluorine, chlorine or bromine together with a pharmaceutical diluent. They are employed orally as tablets, powders, pills or capsules, parenterally as solutions and aqueous suspensions, and topically as creams, lotions with or without coacting antibiotics e.g. penicillins, tetracycline, bacitracin, novobiocin, erythromycin polymyxin B sulphate, gramicidin, streptomycin sulphate, dihydrostreptomycin, and chloramphenicol. Examples describe an eye-ear drop composition containing 6a ,16a -dimethyl-9a -fluoro-11b ,17a -dihydroxy - 1,4 - pregnadiene - 3,20 - dione and an ointment containing 6a ,16a -dimethyl-9a -fluoro - 11b ,17a - dihydroxy - 1,4 - pregnadiene-3,20-dione 17-acetate. Specifications 898,291, 898,293 and 898,294 are referred to.